Attenuated Joint Tissue Damage Associated With Improved Synovial Lymphatic Function Following Treatment With Bortezomib in a Mouse Model of Experimental Posttraumatic Osteoarthritis

Arthritis & Rheumatology
Wensheng WangLianping Xing

Abstract

To investigate the roles of the synovial lymphatic system in the severity and progression of joint tissue damage and functional responses of synovial lymphatic endothelial cells (LECs) to macrophage subsets, and to evaluate the therapeutic potential of the proteasome inhibitor bortezomib (BTZ) in a mouse model of experimental posttraumatic osteoarthritis (OA). C57BL/6J wild-type mice received a meniscal ligamentous injury to induce posttraumatic knee OA. Lymphangiogenesis was blocked by a vascular endothelial growth factor receptor 3 (VEGFR-3) neutralizing antibody. Synovial lymphatic drainage was examined by near-infrared imaging. Joint damage was assessed by histology. RNA-sequencing and pathway analyses were applied to synovial LECs. Macrophage subsets in the mouse synovium were identified by flow cytometry and immunofluorescence staining. M1 and M2 macrophages were induced from mouse bone marrow cells, and their effects on LECs were examined in cocultures in the presence or absence of BTZ. The effects of BTZ on joint damage, LEC inflammation, and synovial lymphatic drainage were examined. Injection of a VEGFR-3 neutralizing antibody into the joints of mice with posttraumatic knee OA reduced synovial lymphatic drainage and a...Continue Reading

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Citations

Nov 15, 2019·Current Opinion in Rheumatology·Anusha RatneswaranMohit Kapoor
May 18, 2020·The Journal of Pathology·Hua WangWen Sun
Dec 1, 2019·Aging·Gaurav Baranwal, Joseph M Rutkowski
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Feb 20, 2021·Journal of Experimental Pharmacology·Gundula Schulze-Tanzil
Apr 12, 2021·Arthritis Research & Therapy·Xiaobo ZhuOscar K Lee

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